In biomedicine, clinicians and researchers now face formidable challenges in information management, innovation, and decision-making in an era which is seeing extraordinarily rapid growth of knowledge, distributed among a host of databases, and on a scale far larger than can be mastered by an individual. The remarkable speed, memory capacity, and symbol-manipulating power of computers, if properly harnessed, can complement human cognitive strengths so as to enable efficient use of all of the knowledge relevant to solution of clinical and scientific problems. To invigorate research in the arena of computation and cognition, a number of fresh concepts have arisen in recent years: computational intelligence, machine learning, intelligence amplifying systems, flexible competence, human-computer collaboration, and computational thinking. As part of its [unreadable]Medical Advanced Research Projects Initiative,[unreadable] the NLM is funding novel approaches to computational thinking, in order to evaluate the feasibility of using innovative computational approaches to enhance the ability of clinicians and biomedical scientists to solve one or more significant cognitive tasks and bring improvements in medical care to patient, families and the public.